Glycogen Flashcards
1
Q
Liver glycogen stores
A
- Glycogen is stored in the fed state to maintain blood glucose when needed
- Depleted during a fasted state after 12-18 hours
2
Q
Glycogen
A
- Glycogenin protein w/ alpha 1,4 glucose chains and alpha-1,6 branch points
- Glycogenin serves as a primer by glucosylating itself (autoglucosylation). That is, glycogenin via a –OH groups of tyrosine within its structure makes a bond to a glucose. The glucose on glycogenin then further elongates the polysaccharide chain
- The anomeric carbon that is not attached to another glycosyl residue (the reducing end) is attached to the protein glycogenin by a glycosidic bond via the amino acid tyrosine.
3
Q
Muscle glycogen stores
A
- Glycogen is stored to provide energy during prolonged exercise
- Not affected by short periods of fasting (a few days) and moderately depleted in prolonged fasting (weeks)
4
Q
Glycogen synthase
A
- transfers the glucose in UDP glucose to one of the growing glycogen branches forming α-1,4 linkages
- G6P allosterically partially activates the inactive (phosphorylated) form of glycogen synthase.
- If glucose levels ⬆️⬆️ in the cell and glycolysis/TCA is going at top speed, but not keeping up with demand, G6P levels⬆️; backup occurs at glycogen synthase
5
Q
Branching enzyme, 4:6 transferase
A
- When about 11 glucose molecules are added to one growing chain of glycogen this enzyme moves a chain of 6-8 glucose molecules to form a new branch chain starting with an α-1,6 linkage at the branch
6
Q
Glycogen Storage Disease Type 0 (GSD 0) molecular basis
A
- A deficiency in the enzyme glycogen synthase results in very low amounts of glycogen stored in the liver. A person between meals can develop hypoglycemia
7
Q
Glycogen Storage Disease Type 0 (GSD 0) symptoms
A
- drowsiness, vomiting, fatigue and sometimes convulsions, and look pale
- muscle cramps from accumulated lactic acid
- mild growth delay
8
Q
Glycogen Storage Disease Type 0 (GSD 0) diagnosis
A
- liver biopsy will show very little glycogen. DNA testing is available
9
Q
Glycogen Storage Disease Type 0 (GSD 0) treatments
A
- snacks every 3-4 hours
- Uncooked cornstarch can act as a ‘slow release’ form of glucose and may prevent hypoglycemia overnight
- A diet higher than normal in protein may help with the cramping, tiredness and fatigue
- affects both males and females
10
Q
Andersen disease (GSD IV) molecular basis
A
- Deficient activity of the glycogen-branching enzyme
- accumulation of abnormal glycogen in the liver, muscle and other tissues
- autosomal recessive
11
Q
Andersen disease (GSD IV) symptoms
A
- In the perinatal variant usually symptoms become apparent in the first few months of a baby’s life
- failure to thrive - slow growth and failure to gain weight at the expected rate
- abnormally enlarged liver and spleen
- progressive liver scarring and liver failure
12
Q
Andersen disease (GSD IV) treatment
A
- very severe but rare disorder
- liver transplantation
- Most children with this condition die before two years of age
13
Q
Adult Polyglucosan Body Disease (APBD) molecular basis
A
- deficient glycogen- branching enzyme activity, diffuse CNS and peripheral nervous system dysfunction
14
Q
Major principles of metabolic regulation
A
- Maximize the efficiency of fuel utilization by preventing the simultaneous operation of opposing pathways (i.e., futile cycles).
- Partition metabolites appropriately between alternative pathways.
- Draw on the fuel best suited for the immediate needs of the organism.
- Shut down biosynthetic pathways when their products accumulate.
15
Q
What are the physiological effects of insulin on the cell?
A
- a phosphatase removes a phosphate group on the enzymes and proteins in cells (Covalent modification by dephosphorylation)
- Insulin, via an insulin factor, activates phosphatases to remove phosphate groups from glycogen phosphorylase, thus INACTIVATING glycogen breakdown
- Insulin, via an insulin factor, activates phosphatases to remove phosphate groups from glycogen synthase, thus ACTIVATING glycogen synthesis
- stimulates the uptake of glucose by muscle (Glut-4)
- When ↑glucose, ↑insulin, ↓glucagon, phosphatases are active
- stimulates glycogen synthesis
16
Q
Glycogen phosphorylase
A
- removes one glucose molecule at a time and converts it to glucose-1-P
- cannot remove glucose within 4 residues of a branch point (α-1,6 linkage)
17
Q
Debranching enzyme
A
2 independent active sites catalyzing transferase and glucosidase reactions:
- 4:4 transferase activity
- glucosyl transferase
- removes the three glucose residues (as a trisaccharide) adjacent to the branch point (the α-1,6 linkage) and transfers them to the end of another row
- 4:4 transferase because the enzyme breaks an α−1,4 bond and forms
another α−1,4 bond
- 1:6 glucosidase activity
- α-1,6-glucosidase or amylo-6-glucosidase
- removes the α-1,6 glucosidic bond to release one glucose molecule as glucose
18
Q
Lysosomal degradation of glycogen
A
- Approximately1-3% of glycogen is degraded by lysosomal enzyme α(1→ 4)- glucosidase
- involved in debranching and hydrolysis of both α-1,4- and α-1,6-glucosidic linkages at acidic PH of 5 and necessary to break down glycogen
19
Q
Glycogen Storage Disease (GSD) generalities
A
- genetic disorders characterized by accumulation of abnormal amounts of glycogen primarily due to decreased degradation
- Synthesis of glycogen occurs in liver and muscle (also minor storage in kidney and intestine) so the GSDs have their primary effect on liver, muscle, RBC, or all
20
Q
Pompe disease (GSD II) molecular basis
A
- deficiency of α(1→ 4) glucosidase or α-1,6-glucosidase or acid maltase
- deficiency in this enzyme results in accumulation of excess amounts of glycogen (normal structure)
